Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over five hundred alkaloids have been identified in extracts from amphibian skins. These include batrachotoxins, which are potent activators of sodium channels, histrionicotoxins, which are noncompetitive blockers of nicotinic receptor-channels and potassium channels, pumiliotoxins/allopumiliotoxins and related homopumiliotoxins, which have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, an extremely potent and selective nicotinic agonist with potent antinociceptive activity. Further alkaloids include decahydroquinolines, pyrrolizidines, indolizidines, quinolizidines, an unprecedented class of disubstituted azabicylo[5.3.0]decanes (lehmizidines), and a variety of tricylic alkaloids, including pyrrolizidine oximes, gephyrotoxins, pseudophrynamines, cyclopentaquinolizidines, coccinellines and coccinelline analogs. Many of the alkaloids are noncompetitive blockers of nicotinic receptor channels. Lipophilic alkaloids occur in skins from four genera of neotropical dendrobatid frogs, in skins from one genus of Australian myobatrachid frogs, one genus of South American bufonid toads and one genus of Madagascan mantellid frogs. It had appeared that all frog skin alkaloids have a dietary origin (ants, beetles, millipedes and other arthropods), being taken up and sequestered unchanged into skin glands. The uptake system appears highly conserved for three of the four family groups that contain skin alkaloids, with respect to alkaloid substrates. But it now appears that pseudophrynamines, a class of indolic alkaloids found only in myobatrachid frogs of Australia, are produced by the frogs themselves, while their uptake system appears to be selective for certain pumiliotoxins/allopumiliotoxins, the only other class of alkaloids found in skin of these frogs. Structures are under investigation for further novel alkaloids. Batrachotoxins also occur in skin and feathers of certain birds.